Lightning in a bottle: The history of platinum-based mesothelioma drugsMost patients with malignant pleural mesothelioma (MPM) receive the same initial chemotherapy cocktail, a blend of two drugs: cisplatin and pemetrexed. According to the American Cancer Society, this mixture is the current "gold standard" for MPM treatment.
Pemetrexed is a recent development. Designed in 2004, its mechanism is simple: It causes a huge drop in the body's levels of folic acid and vitamin B12, which makes it hard for fast-replicating cells (like those in tumors) to multiply.
But what about cisplatin? As its name hints, it's a molecule based around a platinum atom, but how does this treat mesothelioma?
A treatment that's older than you might think
In a recent report, Italian researchers discussed platinum-based "metallo-drugs" in general. These compounds are quite varied - some are new and others old, and their molecular structures all differ considerably - but there's one thing they all have in common.
They're extremely toxic.
The oldest of the "-platins" is cisplatin, a compound first discovered in 1845 by Italian chemist Michel Peyrone. For years, it carried the name "Peyrone's salt," and its uses were almost totally unclear.
As Chemical and Engineering News (CEN) notes, cisplatin languished in obscurity for more than a century after its discovery. It wasn't until the 1960s that it emerged as something special.
A lightning bolt (between platinum electrodes)
At that time, Michigan State University's Dr. Barnett Rosenberg was experimenting with electricity and bacteria. He found that running a current through E. coli in a dish produced a curious effect: bacteria that grew to 300 times their usual size.
After some investigation, Rosenberg and his colleagues had an epiphany. As noted in the CEN article, they found that what was preventing the bacteria from cleaving their DNA (and then separating) was a compound formed when the platinum electrodes were electrified in solution: cisplatin.
The inventive Rosenberg had an idea. If cisplatin can prevent bacterial multiplication, could it hinder tumor growth too? After injecting mice with the substance, he found that it could.
Cisplatin-as-chemotherapy was born. Today, the drug's effectiveness has earned it a reputation as the "penicillin of cancer drugs."
How does it work? Researchers found that it ties tumor DNA in knots - literally. Cisplatin binds tightly to DNA, causing crosslinking between different strands. This knotting leads to cell death, effectively slowing the growth of mesothelioma and other cancers.
Scientists try to predict survival after surgery for advanced mesothelioma, http://ejcts.oxfordjournals.org/content/early/2012/12/12/ejcts.ezs648.abstract, 12/21/12
Study reviews two chemotherapy regimens for operable mesothelioma, http://ar.iiarjournals.org/content/32/12/5393.full.pdf+html, 12/11/12
Study: Multimodal therapy for mesothelioma should be tailored to each patient, http://icvts.oxfordjournals.org/content/early/2012/11/21/icvts.ivs465.full, 11/30/12
Response to chemotherapy may identify candidates for mesothelioma surgery, http://annonc.oxfordjournals.org/content/early/2012/11/06/annonc.mds537.short, 11/29/12
Tomotherapy may be safe for mesothelioma patients after surgery, http://journals.lww.com/jto/Abstract/2012/12000/Tomotherapy_after_Pleurectomy_Decortication_or.18.aspx, 11/29/12
Chemotherapy delivery through thigh may help mesothelioma patients, http://radiology.rsna.org/content/early/2012/11/09/radiol.12111858.abstract, 11/21/12
Researchers compare outcomes of mesothelioma surgeries, http://art.torvergata.it/handle/2108/72282, 11/20/12
Mesothelioma treatment receives orphan drug designation, http://www.morphotek.com/news-events/News-Archive/2012-News/FDA-Grants-Orphan-Drug-Status-to-Morphotek-s-Amatu.aspx, 11/14/12